Predicting in-hospital length of stay for very-low-birth-weight preterm infants using machine learning techniques.

BACKGROUND/PURPOSE: The in-hospital length of stay (LOS) among very-low-birth-weight (VLBW, BW < 1500 g) infants is an index for care quality and affects medical resource allocation. We aimed to analyze the LOS among VLBW infants in Taiwan, and to develop and compare the performance of different LOS prediction models using machine learning (ML) techniques. METHODS: This retrospective study illustrated LOS data from VLBW infants born between 2016 and 2018 registered in the Taiwan Neonatal Network. Among infants discharged alive, continuous variables (LOS or postmenstrual age, PMA) and categorical variables (late and non-late discharge group) were used as outcome variables to build prediction models. We used 21 early neonatal variables and six algorithms. The performance was compared using the coefficient of determination (R2) for continuous variables and area under the curve (AUC) for categorical variables. RESULTS: A total of 3519 VLBW infants were included to illustrate the profile of LOS. We found 59% of mortalities occurred within the first 7 days after birth. The median of LOS among surviving and deceased infants was 62 days and 5 days. For the ML prediction models, 2940 infants were enrolled. Prediction of LOS or PMA had R2 values less than 0.6. Among the prediction models for prolonged LOS, the logistic regression (ROC: 0.724) and random forest (ROC: 0.712) approach had better performance. CONCLUSION: We provide a benchmark of LOS among VLBW infants in each gestational age group in Taiwan. ML technique can improve the accuracy of the prediction model of prolonged LOS of VLBW.

Six-monthly palivizumab prophylaxis effectively reduced RSV-associated hospitalization rates of preterm infants in a subtropical area: a population-based cohort study.

BACKGROUND: To evaluate the effects of 6-monthly palivizumab on respiratory syncytial virus-associated hospitalization (RSVH) in preterm infants in an area without RSV seasonality. METHODS: RSV prophylaxis with 6-monthly palivizumab in infants born at gestational age (GA) ≤28 weeks or those born at GA 29-35 weeks with bronchopulmonary dysplasia (BPD) was implemented in Taiwan since 2010. RSVH, use of mechanical ventilation (MV), admission to intensive care unit (ICU), length of hospital stay, and annual mortality were compared between the historical control group (no prophylaxis, 2008-2009) and the prophylaxis group (2011-2013). RESULTS: The annual RSVH rates decreased in the target population and in subgroups of infants who received prophylaxis (all target infants: odds ratio [OR], 0.43; 95% confidence interval [CI], 0.29-0.65). No difference was observed in MV and ICU usage and 1-year mortality in the ≤28 weeks subgroup. In the GA 29-35 weeks with BPD subgroup, ICU usage and 1-year mortality rates were significantly reduced with palivizumab prophylaxis regimen. A significant decrease was noted in the annual mortality and ICU admission rates of infants who received prophylactic treatment. CONCLUSION: Six-monthly palivizumab treatment reduced the RSVH rate, ICU usage, and annual mortality rates of target infants in an area without RSV seasonality.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

The enhancement of biofilm formation in Group B streptococcal isolates at vaginal pH.

Group B streptococcus (GBS) is a common asymptomatic colonizer in acidic vagina of pregnant women and can transmit to newborns, causing neonatal pneumonia and meningitis. Biofilm formation is often associated with bacterial colonization and pathogenesis. Little is known about GBS biofilm and the effect of environmental stimuli on their growth along with biofilm formation. The objective of this study was to investigate the survival and biofilm formation of GBS, isolated from pregnant women, in nutrient-limited medium under various pH conditions. Growth and survival experiments were determined by optical density and viable counts. Crystal violet staining, scanning electron microscopy, and atomic force microscopy (AFM) were used to analyze the capacity of biofilm production. Our results showed that GBS isolates proliferated with increasing pH with highest maximum specific growth rate (µmax) at pH 6.5, but survived at pH 4.5 for longer than 48 h. Biofilm formation of the 80 GBS isolates at pH 4.5 was significantly higher than at pH 7.0. This difference was confirmed by two other methods. The low elastic modulus obtained from samples at pH 4.5 by AFM revealed the softness of biofilm; in contrast, little or no biofilm was measured at pH 7.0. Under acidic pH, the capability of biofilm formation of serotypes III and V showed statistically significant difference from serotypes Ia and Ib. Our finding suggested that survival and enhanced biofilm formation at vaginal pH are potentially advantageous for GBS in colonizing vagina and increase the risk of vaginosis and neonatal infection.

The role of glucocorticoid receptors in dexamethasone-induced apoptosis of neuroprogenitor cells in the hippocampus of rat pups.

BACKGROUND: Dexamethasone (Dex) has been used to reduce inflammation in preterm infants with assistive ventilation and to prevent chronic lung diseases. However, Dex treatment results in adverse effects on the brain. Since the hippocampus contains a high density of glucocorticoid receptors (GCRs), we hypothesized that Dex affects neurogenesis in the hippocampus through inflammatory mediators. METHODS: Albino Wistar rat pups first received a single dose of Dex (0.5 mg/kg) on postnatal day 1 (P1) and were sacrificed on P2, P3, P5, and P7. One group of Dex-treated pups (Dex-treated D1D2) was given mifepristone (RU486, a GCR antagonist) on P1 and sacrificed on P2. Hippocampi were isolated for western blot analysis, TUNEL, cleaved-caspase 3 staining for cell counts, and morphological assessment. Control pups received normal saline (NS). RESULTS: Dex reduced the developmental gain in body weight, but had no effect on brain weight. In the Dex-treated D1D2 group, apoptotic cells increased in number based on TUNEL and cleaved-caspase 3 staining. Most of the apoptotic cells expressed the neural progenitor cell marker nestin. Dex-induced apoptosis in P1 pups was markedly reduced (60%) by pretreatment with RU486, indicating the involvement of GCRs. CONCLUSION: Early administration of Dex results in apoptosis of neural progenitor cells in the hippocampus and this is mediated through GCRs.

Urban-Rural Disparity in the Incidence of Diagnosed Autism Spectrum Disorder in Taiwan: A 10-Year National Birth Cohort Follow-up Study.

Autism spectrum disorder (ASD) is reportedly more prevalent in urban areas partly because of better accessibility and affordability to healthcare. With universal health insurance coverage in Taiwan, a previous study has shown no urban-rural disparity in the utilization rate of a child's preventive healthcare. Under this circumstance, we followed a birth cohort of 176,273 live births from 2006 to 2015 to detect the differences in ASD incidence between urbanicities. After adjusting for socioeconomic factors, children were 1.28 (95% confidence interval (CI): 1.13-1.44) and 1.54 (95% CI: 1.36-1.75) more likely to acquire ASD in satellite and urban areas compared with those in rural areas, respectively. A gradient association between parental educational attainment and ASD incidence was also noted. Greater ASD incidences in more urbanized areas and more advanced educated parents' children were detected under a circumstance with low barriers to healthcare.

Machine learning to predict late respiratory support in preterm infants: a retrospective cohort study.

Bronchopulmonary dysplasia (BPD) has been a critical morbidity in preterm infants. To improve our definition and prediction of BPD is challenging yet indispensable. We aimed to apply machine learning (ML) to investigate effective models by using the recently-proposed and data-driven definition to predict late respiratory support modalities at 36 weeks' post menstrual age (PMA). We collected data on very-low-birth-weight infants born between 2016 and 2019 from the Taiwan Neonatal Network database. Twenty-four attributes associated with their early life and seven ML algorithms were used in our analysis. The target outcomes were overall mortality, death before 36 weeks' PMA, and severity of BPD under the new definition, which served as a proxy for respiratory support modalities. Of the 4103 infants initially considered, 3200 were deemed eligible. The logistic regression algorithm yielded the highest area under the receiver operating characteristic curve (AUROC). After attribute selection, the AUROC of the simplified models remain favorable (e.g., 0.801 when predicting no BPD, 0.850 when predicting grade 3 BPD or death before 36 weeks' PMA, and 0.881 when predicting overall mortality). By using ML, we developed models to predict late respiratory support. Estimators were developed for clinical application after being simplified through attribute selection.

Postnatal corticosteroid treatment as a risk factor for false positivity in severe combined immunodeficiency newborn screening.

From 2011, 37 children were referred to a hospital due to low levels of T cell receptor excision circles (TRECs) from newborn screening. Among them, three children were immunologically characterized and followed up to show that postnatal corticosteroid usage may be among the causes of false positivity in TRECs screening.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

Neonatal and infant mortality of very-low-birth-weight infants in Taiwan: Does the level of delivery hospital matter?

BACKGROUND: To study the distribution of the birthplaces of very-low-birth-weight (VLBW) infants and examine whether delivery at different levels of hospital affects neonatal and infant mortality. METHODS: This population-based cohort study was retrieved from Taiwan Maternal and Child Health Database. Livebirth singleton VLBW infants born between 2011 and 2014, with BW between 500 and 1499 g and gestational age ≥22 weeks were enrolled. The main outcomes were risk-adjusted odds ratios (aOR) of neonatal and infant mortality by birthplace, which was categorized as medical center (MC), regional hospital (RH), district hospital (DH), and clinic (C) based on Taiwan's hospital accreditation system. RESULTS: Of 4560 VLBW infants enrolled, 3005 (66%) were born in MCs, 1181 (26%) in RHs, 213 (5%) in DHs, and 161 (4%) in Cs. Neonatal mortality rates were 10%, 15%, 16%, 17%, and infant mortality rates were 13%, 17%, 18%, 21%, if born in MCs, RHs, DHs and Cs, respectively. The aORs for neonatal and infant mortality were 1.94 (95% CI 1.53-2.48) and 1.67 (1.34-2.08) for those born in RHs, 2.26 (1.38-3.70) and 1.82 (1.16-2.86) for infants born in DHs/Cs, as compared to those born in MCs. For VLBW infants born in RHs, DHs, and Cs and postnatally transferred to MCs, the aORs of neonatal and infant mortality were lower than those who were not transferred. CONCLUSION: VLBW infants born outside of MCs had higher neonatal and infant mortality and a two-fold higher risk of mortality than those born in MCs. When possible, VLBW infants should be born in MCs.

Respiratory Trajectory after Invasive Interventions for Patent Ductus Arteriosus of Preterm Infants.

Invasive interventions have been conducted in preterm infants with significant patent ductus arteriosus (PDA) when medical treatment has failed, and methods of invasive intervention have been reported. Surgical ligation via lateral thoracotomy has been a well-established procedure for decades. Recently, transcatheter occlusion has been safely and feasibly applied to the premature population. However, little research has been conducted on the benefits of transcatheter occlusion in very-low-birth-weight (VLBW) infants compared to surgical ligation. This study compared transcatheter and surgical techniques in VLBW infants in terms of short-term respiratory outcomes. The medical records of 401 VLBW infants admitted to a tertiary hospital between September 2014 and January 2019 were retrospectively reviewed. Patients who were diagnosed with a congenital anomaly, a chromosomal anomaly, or congenital heart disease, except for an inter-atrial shunt, were excluded. The perinatal conditions, neonatal morbidities, periprocedural vital signs, and respiratory support trajectories were compared between the transcatheter-treated and surgically ligated group. A total of 31 eligible VLBW infants received invasive intervention: 14 were treated with transcatheter occlusion (Group A), and 17 infants were treated with surgical ligation (Group B). Respiratory outcomes were not statistically significant between the two groups, despite Group A showing a trend toward early improvement in post-intervention respiratory trajectory. In this small case study, a different trend in post-intervention respiratory trajectories was observed. Future research with larger case numbers should be conducted to address our preliminary observations in more detail.

Compliance with dosing recommendations from common references in prescribing antibiotics for preterm neonates.

PURPOSE: Incorrect dosage was the most common type of medication errors in neonate patients. Different dosing recommendations from common reference sources may have contributed to the errors. This study assesses the compliance rate with the common reference sources in antibiotic dosage prescribed for preterm infants in a neonatal intensive care unit (NICU). METHODS: A retrospective study using chart review was conducted at a tertiary care medical center with university affiliation in Taiwan. Study subjects were preterm neonates admitted to the NICU of the medical center between 2000 and 2002 and prescribed at least one antibiotic during the stay. Recommendations from three commonly used reference sources (Pediatric Dosage Handbook, Neonatal Drug Formulary, and Neofax) were employed to evaluate the dosage compliance of the antibiotic prescriptions. RESULTS: A total of 433 preterm infants and 3459 prescriptions were included. Depending on the reference source used, the percentages of antibiotic prescriptions where both the dose and the interval were compliant with recommendations ranged from 36.88 to 87.54%. CONCLUSIONS: A significant proportion of antibiotics prescribed for preterm neonates in this medical center did not comply with the recommended dosage from common reference sources. Future studies should investigate the clinical impacts of the dosing deviation.

Transcutaneous bilirubin nomogram for Taiwanese newborns - A single center study.

BACKGROUND: Hour-specific bilirubin nomogram has been recommended to predict postdischarge hyperbilirubinemia in newborns. However, it may not be applicable in Taiwan due to ethnic differences. The aim of this study was to construct a 12-h specific transcutaneous bilirubin (TCB) nomogram in newborns for clinical reference. METHODS: We prospectively enrolled full term or late preterm neonates born in a tertiary care hospital between October 2013 and July 2014. The exclusion criteria included chromosome anomaly, glucose-6-phosphate dehydrogenase deficiency, and receiving phototherapy within 60 h after birth. TCB measurements were performed by a single technician using the Bilichek device, and measured every 12 h until neonates were discharged. Patient data including sex, delivery mode, gestational age, body weight with daily change, and feeding pattern were collected for analysis. A TCB nomogram was constructed with 40th, 75th, and 95th percentile lines. RESULTS: A total of 498 newborns were enrolled, and the characteristics between the hyperbilirubinemia and nonhyperbilirubinemia groups were not different. The mean TCB curve revealed that the peak TCB level was 14.2 ± 2.9 mg/dL at 100.6 ± 3.6 h of age. The peak 95th percentile TCB level was 19.4 mg/dL at 121.9 ± 5 h of age. Mean TCB levels increased at a rate of 0.01-0.21 mg/dL/h initially, followed by a decrease after 96-108 h of age. Twenty newborns (4%) were diagnosed with hyperbilirubinemia. Regarding TCB distribution, 11 of 60 (18%) had peak TCB levels above the 95th percentile, 5 of 151 (3%) had TCB levels between the 75th and 95th percentile, 4 of 200 (2%) had levels between the 40th and 75th percentiles, and none had a level below the 40th percentile. CONCLUSION: A 12-h specific TCB nomogram could be a useful reference for workup for hyperbilirubinemia, particularly when it is above the 95th percentile line.

Comparing regional neonatal mortality rates: the influence of registration of births as live born for birth weight <500 g in Taiwan.

OBJECTIVE: To investigate regional variation in the registration of births (still+live) as live born for birth weight <500 g and the impact on the city/county ranking of neonatal mortality rate (NMR) in Taiwan. DESIGN: Population-based cross-sectional ecological study. SETTING: 20 cities/counties in Taiwan. PARTICIPANTS: Registered births for birth weight <500 g and neonatal deaths in 2015-2016. MAIN OUTCOME MEASURES: City/county percentage of births <500 g registered as live born and ranking of city/county NMR (deaths per 1000 live births) including and excluding live births <500 g. RESULTS: The percentage of births <500 g registered as live born ranged from 0% in Keelung City (0/26) and Penghu County (0/4) to 20% in Taipei City (112/558), 24% in Hsinchu County (5/21) and 28% in Hualien County (9/32). The change in city/county ranking of NMR from including to excluding live births <500 g was most prominent in Taipei City (from the 15th to the 1st) followed by Kaohsiung City (from the 18th to the 14th). CONCLUSIONS: The city/county NMR in Taiwan is influenced by variation in the registration of live born for births with uncertain viability. We recommend presenting city/county NMR using both criteria (with or without minimum threshold of gestation period or birth weight) for better interpretation of the findings of comparisons of city/county NMR.

Seasonal peaks and risk factors of respiratory syncytial virus infections related hospitalization of preterm infants in Taiwan.

OBJECTIVES: To assess the nationwide seasonal peaks, risk factors, and utilization of medical resources of respiratory syncytial virus-associated hospitalization (RSVH) in preterm infants in Taiwan. STUDY DESIGN: A Taiwan nationwide birth cohort was extracted from the Birth Certificate Application Database during 2007-2009 and prospectively linked to the National Health Insurance database. We evaluated the seasonal peaks and risk factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with the RSVH of preterm infants. The length of hospital stays (LOS), care in intensive care unit (ICU), and use of mechanical ventilation (MV) were also analyzed. RESULTS: There is a total duration of 9 months of RSVH season in Taiwan, three seasonal peaks and two seasonal peaks of RSVH in preterm infants with BPD and without BPD, respectively. Preterm infants had significantly higher RSVH rate than term infants (2.6% vs 0.9%, p<0.0001). Preterm infants born at 29-35 weeks of gestational age (wGA) with BPD had significantly higher RSVH rate than those without BPD (p<0.0001). Preterm infants without BPD born at < 32 wGA had higher RSVH rate than those born at 33-35 wGA (p<0.0001). Overall, 56.4% of RSVH occurred within 9 months of CA. Preterm infants with BPD had significantly higher ICU admission rate within 18 months of CA (p<0.0001), MV usage within 12 months of CA (p<0.0001) and LOS within 18 months of CA (p<0.001) than those without BPD. RSVH occurred within 6 months of CA was significantly associated with higher ICU admission rate (p<0.0001), MV usage (p = 0.0002) and longer LOS (p<0.001) in preterm infants without BPD. CONCLUSIONS: There is a total duration of 9 months of RSVH season in Taiwan. Preterm < 32 wGA, BPD, and CA within 6 months were risk factors of RSVH which also contribute to higher utilization of medical resources.

Effect of a Delayed Start to Oral Feeding on Feeding Performance and Physiological Responses in Preterm Infants: A Randomized Clinical Trial.

BACKGROUND: The efficient and safe oral feeding of preterm infants, an essential criterion for hospital discharge, is affected by neurodevelopmental maturation. However, the timing of initiating oral feeding and its relation to maturation, feeding performance, and physiological responses are unclear. PURPOSE: The aim of this study was to determine the effect of a 1-week delay in the initiation of oral feeding on feeding performance, transition time, weight gain, and cardiorespiratory responses in preterm infants. METHODS: In this randomized controlled trial, 40 infants with a gestational age at birth of less than 32 weeks were recruited. The control group (n = 18) began oral feeding when the infants were physiologically stable, whereas the experimental group (n = 22) began oral feeding 1 week later. Infant feeding performance, heart rate, and oxygen saturation were measured before, during, and after feeding on the first day of oral feeding and 3 days later. Daily weight gain was calculated by measuring body weight every morning, and transition time was calculated by counting the number of days from the initiation of oral feeding to the termination of tube feeding. RESULTS: There were no significant differences between the two groups in terms of feeding performance, weight gain, or postmenstrual age at the completion of full oral feeding. The transition time was significantly shorter in the experimental group than in the control group. More infants in the control group experienced episodes of oxygen desaturation during feeding than in the experimental group. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: For infants with a postmenstrual age of greater than 32 weeks who are ready to initiate oral feeding, postponing oral bottle feeding for 1 week may be considered as an intervention to reduce physiological distress.

Effects of single-hole and cross-cut nipple units on feeding efficiency and physiological parameters in premature infants.

The purpose of this study was to compare the amount of total milk intake, feeding time, sucking efficiency, heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) of premature infants when fed with either signal-hole or cross-cut nipple units. Twenty stable infants admitted to a level II nursery in a tertiary care center with gestational ages averaging 32.2+/-3.2 wks were enrolled. Subjects had an average postmenstrual age of 34.1+/-1.6 wks, and average body weight of 1996+/-112 gm. A crossover design was used and infants were observed for two consecutive meals separated by a four-hour interval. They were bottle fed with equal feeding amounts using a single-hole and cross-cut nipple administered in random order. Results showed that infants fed with single-hole nipple units took more milk (57.5+/-8.3 ml vs. 51.6+/-9.5 ml, p=.011), had a shorter feeding time per meal (11.5+/-4.9 min vs. 20.9+/-5.0 min, p<.001), and sucked more efficiently (5.8+/-2.5 ml/min vs. 2.7+/-1.0 ml/min, p<.001) compared to those fed through cross-cut nipples. Infants using cross-cut nipple units had a higher RR (44.4+/-4.6 breaths/minutes vs. 40.8+/-4.9 breaths/minutes, p=.002) and SpO2 (96.1+/-1.4% vs. 94.6+/-3.2%, p=.044) than those using single-hole nipples. Oxygen desaturation (SpO2<90% and lasting for longer than 20 sec) and bradycardia were not recorded in either group of infants during feeding. Compared to using cross-cut nipple units, premature infants using single-hole nipple units take more milk and tend to tolerate feedings better. A single-hole nipple may be a choice for physiologically stable bottle-fed premature infants.

Randomized Trial to Compare Renal Function and Ductal Response between Indomethacin and Ibuprofen Treatment in Extremely Low Birth Weight Infants.

BACKGROUND: A head to head comparison study on renal function and ductal response between indomethacin and ibuprofen has rarely been conducted in extremely low birth weight (ELBW) infants. OBJECTIVES: The aim was to compare renal function and ductal response between indomethacin and ibuprofen in ELBW infants. METHODS: We performed a double-blind randomized control trial to compare renal function and ductal response between indomethacin (0.2, 0.1, and 0.1 mg/kg i.v. every 24 h for 3 doses) and ibuprofen lysine (10, 5, and 5 mg/kg i.v. every 24 h for 3 doses) in ELBW infants with significant hemodynamic patent ductus arteriosus (cardiovascular dysfunction score >3 and LA/AO ratio ≥1.3). RESULTS: A total of 144 infants were enrolled: 73 received indomethacin and 71 received ibuprofen lysine. Significant decreases in urine output were seen in 30 infants (41%) in the indomethacin group and 15 (21%) in the ibuprofen group (p = 0.02). The indomethacin group was associated with a significantly higher chance of persistent ductal response than the ibuprofen group (66 vs. 49%, p = 0.046), but with a lower glomerular filtration rate on day 1, higher serum creatinine on days 1, 2, and 7, and lower urinary prostaglandin on days 2-7. Both groups were comparable in mortality and in bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity morbidity. CONCLUSIONS: With the current dosage, ibuprofen had fewer renal side effects but was associated with a lower rate of persistent ductal closure in ELBW infants. The precise role of prostaglandin on renal tubular function in ELBW infants remains to be further investigated.